The purpose of this proposal is to study by newer, direct methods, the pathways for the transport of proteins, polypeptides, and lipoproteins across cells and basement membranes. The studies will be done on isolated segments of renal tubules employing in vitro and in situ microperfusion methods and electron microscopy. Functional, quantitative data on the absorption and transport of various macromolecular substances will be directly correlated with fine structural changes at the subcellular level by autoradiographic and histochemical techniques. By microperfusing macromolecular substances at varying concentrations and time intervals and following fine structural changes in the cells and membranes sequentially, the mechanisms for the absorption, transport or degradation of these substances should be elucidated. Ultimately, it is planned to study transport or macromolecular substances across cells injured by a variety of harmful agents. This information would be of fundamental importance in understanding the role of macromolecules and their transport process during physiological and many pathologic conditions.